Throughout this application, various publications are cited by reference numbers. Full citations for these publications may be found listed at the end of the specification immediately preceding the claims. Certain references and publications are cited by full citation. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
Chronic obstructive pulmonary disease (COPD), consisting of emphysema and chronic bronchitis, is the fourth leading cause of death in the United States (1). Approximately 15 million Americans are affected by COPD and there is an increasing incidence in women(2). Smoking is the major risk factor for COPD and accounts for over 90% of cases seen worldwide. Despite the importance of the disease, there are no specific therapies available to limit or prevent the slow, progressive, destructive changes observed in COPD(3).
Currently the major hypothesis for the pathogenesis of emphysema is the protease-antiprotease theory(4,5). This model suggests that an imbalance between the levels of extracellular matrix degrading enzymes and their respective inhibitors damage the connective tissue matrix components of the lung. Studies over the past 30 years have demonstrated differences in the protease levels in the lung of patients with emphysema when compared to normal lung tissue(6). However, the molecular consequences of this finding have not been determined.
Although studies have demonstrated loss of the extracellular matrix in the lung of patients with emphysema, an investigation as to whether cell death contributes to the pathogenesis of this disease has not been performed.
The present invention provides a method of treating or preventing a chronic obstructive pulmonary disease in a subject, comprising administering to said subject an amount of an agent effective to inhibit apoptosis of the subject""s lung cells and thus treat or prevent chronic obstructive pulmonary disease in the subject. The present invention provides for a method of identifying a compound effective to treat or prevent a chronic obstructive pulmonary disease, comprising (a) contacting lung cells from a subject having a chronic obstructive pulmonary disease with the compound and measuring the level of apoptosis of the lung cells in the presence of said compound, (b) measuring the level of apoptosis of the lung cells from the same subject in the absence of said compound, (c) comparing the level of apoptosis in step (a) with the level of apoptosis in step (b), wherein a higher level of apoptosis in step (a) indicate that the compound is effective to treat or prevent chronic obstructive pulmonary disease.